Platelet adenylate cyclase activation

Ebstein R, Belmaker R, Grunhaus L, et al Lithium inhibition of adrenaline-stimulated adenylate cyclase in humans. Nature 259 411-413, 1976 Ebstein RP, Hermoni M, Belmaker RH The effect of lithium on noradrenahne-in-duced cyclic AMP accumulation in rat brain inhibition after chronic treatment and absence of supersensitivity. J Pharmacol Exp Ther 213 161-167, 1980 Ebstein RP, Lerer B, Shlaufman M, et al The effect of repeated electroconvulsive shock treatment and chronic lithium feeding on the release of norepinephrine from rat cortical vesicular preparations. Cell Mol Neurobiol 3 191-201, 1983 Ebstein RP, Moscovich D, Zeevi S, et al Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity prosreceptor modification or second messenger signal amplification. Psychiatry Res 21 221-228, 1987 Eccleston D, Cole AJ Calcium-channel blockade and depressive illness. Br J Psychiatry 156 889-891, 1990... 

Newman ME, Drummer D, Lerer B Single and combined effects of desimipramine and lithium on serotonergic receptor number and second messenger function in rat brain. J Pharmacol Exp Ther 252 826-831, 1990 Newman ME, Lerer B, Lichtenberg P, et al Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment. Psychopharmacology 109 231-234, 1992... 

Forskolin (5-[acetyloxy]-3-ethenyldodecahydro-6,10,10b-trihydroxy-3,4a,7,7,10a-penta-methyl-[3R- 3a-4aP, SP, 6P, 6aa,10a, lOaP, 10ba -lFf-naphtho[2,l-b]pyran-l-one) [66575-29-9] M 410.5, m 229-232°, 228-233°. Recrystd from CfiH6-pet ether. It is antihypertensive, positive ionotropic, platelet aggregation inhibitory and adenylate cyclase activating properties [Chem AbstrS9 1978 244150, de Souza et al. Med Res Rev 3 201 1983]. 

Anand-Srivastava MB. 1993. Rat platelets from spontaneously hypertensive rats exhibit decreased expression of inhibitory guanine nucleotide regulatory protein relationship with adenylate cyclase activity. Circ Res 173 1032-1039. 

Livingstone, C., A.R. McLellan, M.A. McGregor, A. Wilson, J.M. Connell, M. Small, G. Milligan, K.R. Paterson, and M.D. Houslay. 1991. Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects. Biochim. Biophys. Acta 1096 127-133. 

Hydroxy alkenals affect adenylate cyclase activity and phospholipase C activities reduce cell growth and promote cell differentiation inhibit platelet aggregation block macrophage action block thiol group... 

Alkenals, such as 4-hydroxynonenal (Esterbauer, 1985) which is very biologically active, inhibiting platelet aggregation, activating adenyl cyclase activity (Esterbauer, 1985) and is a substrate for glutathione transferases and... 

Huttemann, E, Ukena, D, Lenschow, V, Sdiwabe, U, Adenosine receptors in human platelets Characterization by 3=-Atethylcarboxamido[ H]adenosine binding in relation to adenylate cyclase activity. Nauyn-Schmiedebergs Arch Pharmacol 1984,32S 226-28S. 

Haslam RJ, Vanderwel M. Inhibition of platelete adenylate cyclase by l-0-alkyl-2-0-acetyl-sn-glyceryl-3-fdiosphoryldioline (platdet-activating factor). J Biol Chon 1982 257 6879-6885 Henson PM. Release of vasoactive amine from rabbit platelets induced by sensitized mmoniidear leukocytes and antigens. J Exp Med 1970 131 287-304... 

De Souza, N. J., Dohadwalla, A. N., and Reden, J., Forskolin a labdane diterpenoid with antihypertensive, positive inotropic, platelet aggregation inhibitory and adenylate cyclase activating properties, Med. Res. Rev. (1983) 3, 201-219. 

ADENYLATE CYCLASE ACTIVATION (PLATELETS AND BLOOD VESSELS)... 

Figure 8.5 PGl2-dependent activation of platelet adenylate cyclase. The data are presented as an Eadie-Hofstee plot, dv is the increase in adenylate cyclase activity above basal enzyme activity, and [L] the PGI2 concentration (nmolL ). (Reproduced from reference 21 with permission)...

Agonist-specific desensitization of prostacyclin-stimulated adenylate cyclase activity has been demonstrated in numerous systems, including human fibroblasts, and platelets in vitro and in vivo ". We have examined the mechanism of desensitization in both human platelets and in cells of the NCB-20 cell line Important and interesting differences have emerged which provide some insights into the events that follow agonist occupation of membrane receptors. 

Figure 8.22 Heterologous desensitization of adenosine (A2) receptors by iloprost. Platelets were incubated for 24 h in the absence (O) or presence ( ) of IO//molL iloprost. Platelet membranes were prepared, and adenylate cyclase activity measured in the absence or presence of NECA (0.1-100/zrnolL ). Results show mean SEM values for the increase in enzyme activity (Sv) (Reproduced from reference 35 with permission)...

Fig. 2A,B. Further separation of two LAP substrates of rat brain by a Mono-Q column (HPLQ. A Elution was performed with linear gradients of 0.1-0.35 M NaQ in 20 mM Tris-HQ (pH 7.5), 1 mM EDTA, 1 mM dithiothreitol, 0.1% Lubrol. B Each fraction was incubated with preactivated A-protomer of lAP and [a- PjNAD ( ), with ( SJGTP7S (A), or with GTP7S and MgQj ( ) at 30°C for 1 h. In the case of , an aliquot of the incubation mixture was further incubated with human platelet membranes and forskolin to measure adenylate cyclase activity of membranes...

Fig. 5.9. Effects of vascular PGI2 receptors, a prototype of adenylate cyclase-linked prostanoid receptors. PGI2 released from endothelial cells interacts with IP receptors (IPR) present on vascular smooth muscle cells and blood platelets. IP receptors stimulate adenylate cyclase activity, which results in vasorelaxation and inhibition of platelet aggregation.

Prostacyclin and its analogues also function by increasing the level of platelet cAMP, presumably by activation of the enzyme adenyl cyclase. A chemically stable analogue of prostacyclin called Iloprost has been effective in preventing consumption of platelets (71). 

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